Clinical nephrology - IgA nephropathy, lupus nephritis, vasculitis

and Aims: To evaluate the efficacy and safety of telmisartan combined with clopidogrelin and/or leflunomide for patients with lgA nephropathy and whether the combination therapy surpass telmisartan in decreasing proteinuria and protecting renal function. Methods:We enrolled 400 patients aged 18-55 years from 13 centers in Beijing who had proteinuria 0.5 ̃3.5g per day, baseline serum creatinine (SCr) <265.2μmol/L (3mg/ dl). All patients were eluted by taking telmisartan 80mg per day for 4 weeks and then randomly assigned to receive at least 24 weeks of treatment with telmisartan 80mg per day + clopidogrelin placebo + leflunomide placebo (group A), telmisartan 80mg per day + clopidogrelin 50mg per day + leflunomide placebo (group B), telmisartan 80mg per day + clopidogrelin placebo + leflunomide 20mg per day (group C), telmisartan 80mg per day + clopidogrelin 50mg per day + leflunomide 20mg per day (group D). Comparison of 24-hr urinary protein excretion, the serum creatinine, eGFR, albumin, cholesterol and uric acid, before and after the therapy were assessed. Results: No statistically significant differences were observed for any baseline clinical data including age, gender, BMI, blood pressure, proteinuria, serum creatinine, eGFR, serum uric acid in the four groups (P>0.05). After treatment for 24 weeks, a significant decline of proteinuria was observed in the four groups (P <0.05), while those in group C (1.20±0.76 vs 0.77±0.42 g/24h) and group D (1.16±0.63 vs 0.74±0.49 g/24h) were decreased more significantly than in group A (1.15±0.87 vs 0.92±0.58 g/24h) and group B (1.11±0.83 vs 0.89±0.42 g/24h) (P<0.05). Mixed effects were showed that telmisartan, leflunomide, and telmisartan combined with leflunomide were effective in lowering proteinuria (P<0.01) by model analysis. The extent of serum creatinine decline in group C and group D displayed more significantly than that in group A and group B (P<0.05). The levels of eGFR in group C and group D were increased more than those in group A and group B. The decline of serum uric acid in group C and group D displayed more significantly than group A and group B (P<0.05). There were no significant differences in the results of albumin and cholesterol among the four groups (P > 0.05). No obvious adverse reactions were found in the four groups. Conclusions: In the selected patients with IgA nephropathy, telmisartan combined with leflunomide was safe and effective in decreasing proteinura and protecting short-term renal function. Larger randomized studies would be needed to confirm these results in the long run.